Sugar Taxes, Lowering Insulin and Age ReversalUpdates on taxes on sugar products, foods that lower insulin levels and age reversal research.http://news-round.com/feeds/4443300474-sugar-taxes-lowering-insulin-and-age-reversal
Thu, 21 Mar 2019 18:33:48 +0000After Mosque Attacks, New Zealand Banning ‘Military-Style’ Gunshttps://www.snopes.com/ap/2019/03/20/after-mosque-attacks-new-zealand-banning-military-style-guns/
Thu, 21 Mar 2019 04:15:47 +0000https://www.snopes.com/ap/2019/03/20/after-mosque-attacks-new-zealand-banning-military-style-guns/Trump to Order Colleges to Back Free Speech or Lose Fundinghttps://www.snopes.com/ap/2019/03/21/trump-to-order-colleges-to-back-free-speech-or-lose-funding/
Thu, 21 Mar 2019 14:40:00 +0000https://www.snopes.com/ap/2019/03/21/trump-to-order-colleges-to-back-free-speech-or-lose-funding/What’s in My Morning Pill?http://sitn.hms.harvard.edu/flash/2019/whats-morning-pill/
Thu, 21 Mar 2019 13:00:35 +0000http://sitn.hms.harvard.edu/?p=15809by Jordan Wilkerson figures by Aparna Nathan Every morning when I wake up, I take a swig of water and swallow a blue pill. I don’t have an illness that the drug is treating. In fact, I’m quite healthy. I take the pill to keep from getting ill. Referred to as PrEP, or Pre-Exposure Prophylaxis, the pill protects me from potential infection by the infamous …

Every morning when I wake up, I take a swig of water and swallow a blue pill. I don’t have an illness that the drug is treating. In fact, I’m quite healthy. I take the pill to keep from getting ill. Referred to as PrEP, or Pre-Exposure Prophylaxis, the pill protects me from potential infection by the infamous virus HIV (Human Immunodeficiency Virus). The main reason I’m on it is because I’m a gay man. By far, the people most affected by HIV in the US have been, and still are, gay and bisexual men. Representing less than 5% of the US population, they accounted for 67% of the 40,000 new HIV diagnoses in 2016. Yet, the Center for Disease Control and Prevention (CDC) also reports that over 600,000 heterosexual Americans have “substantial risks” of contracting the virus and should consider taking PrEP. So what makes HIV dangerous enough to warrant preventative treatment?

Like all viruses, HIV’s goal is simple: replicate. But the difference is that HIV targets cells crucial to our immune system, creating a macabre irony. The immune system exists to thwart viral takeovers, but HIV uses it, instead, to fast-track its deadly spread through our bodies. Upon first making its way into the body, HIV kickstarts mass production of the viruses by attaching itself to an immune cell. The virus then injects two materials that create HIV DNA within the cell: a molecule that has instructions to build the DNA and an enzyme that builds DNA using those instructions (Figure 1). This newly generated viral DNA is then used to trick the cell into producing many more copies of the virus. The outpour of new viruses destroys the cell, and the fresh pack hunts for more immune cells to infect.

Figure 1: Schematic of HIV replication.

The immune system does put up a fight, though. Cells that are not yet infected will even commit suicide in a desperate attempt to stop the viral uprising. But HIV mutates quickly, resulting in many versions of the virus. As a result, the immune system simply can’t keep up with the motley crew of viral strains (this is also why HIV vaccines don’t exist). The battle continues until the cells composing our immune system are so depleted that we cross the threshold from HIV to AIDS (Acquired Immune Deficiency Syndrome). At this point, infections that a healthy immune system could easily quash start posing serious health risks. Without lifelong treatment to impede HIV’s insurgence, death can greet us in under a decade.

PrEP, a combination of the two drugs tenofovir disoproxil fumarate and emtricitabine, stops HIV before the infection can begin. Approved by the Food and Drug Administration (FDA) in July 2012, the treatment targets the DNA-building enzyme that HIV injects into the first cell, rendering it incapable of making DNA (see orange arrow in Figure 1). With sufficient levels of PrEP in the cells, the virus cannot replicate. Once someone already has HIV, however, PrEP is ineffective. But the treatment works quite well at preventing the virus from initially taking hold. PrEP reduces the risk of contracting HIV from sex by over 90%.

Despite this, there are way fewer people taking PrEP than people considered to be at high risk of getting HIV. In the US, just a little over 8% of people at high risk are on the treatment. For Latinos and African Americans, the percentage is even lower (Figure 2). Cost is one barrier. The only PrEP treatment on the market is Truvada, which is produced by Gilead Sciences. Truvada costs almost $2000 for a 30-day supply – kind of expensive. In fairness, Gilead does offer some assistance to help cover co-pays if you have commercial insurance. Another way to drive down cost is market competition. Generic versions sold overseas can be as cheap as $70 a year, and the FDA approved a generic version of the treatment last year for sale in the United States. When this version will actually be available to Americans, though, is uncertain, since Gilead still has patents that preclude competition. In the meantime, some people simply won’t be able to afford the treatment.

Figure 2: Numbers of high-risk individuals compared to those currently on PrEP. Despite more being at high risk, fewer African Americans are on PrEP than white Americans by a factor of 6.

Another barrier may be hesitation from doctors. While most primary care physicians say they’ve heard of PrEP, only about a third have prescribed (or even suggested) the treatment to a patient. One concern is that gay and bisexual men may use PrEP to justify more frequently engaging in risky sexual behavior. This type of concern has also been brought up in other situations, such as increasing access to birth control. The worries turned out to be unfounded for birth control, but PrEP may be another story. A comprehensive look at medical data has found that cases for chlamydia, gonorrhea, and syphilis appear to increase among PrEP users. Most studies also confirmed via questionnaires that PrEP users are having more condomless sex. While this is a problem to be addressed, it’s important to note that unlike HIV, all three of the aforementioned STIs can be treated with a short course of antibiotics.

The spread of other STIs is increasing in communities with widespread PrEP adoption, but what about HIV rates? Does increased PrEP adoption in the gay community simply get negated by more frequent risky sex? Apparently not. A team of scientists examined this question by looking at new HIV diagnoses in the Australian state of New South Wales, where thousands of high-risk men recently started taking PrEP. Published in The Lancet HIV this past November, the research team found a 25% decline in new HIV diagnoses among men who have sex with men just a year after the PrEP rollout, despite decreased condom use. A similar decline for high-risk men in the US was reported at the International AIDS conference last year. Though arguably unsurprising, these findings are a big deal. They demonstrate that government programs that provide free PrEP prescriptions, such as the ones in California and Florida, actually contribute to the larger effort to eradicate HIV entirely. The findings also push back on resisting PrEP adoption based on the behavioral change it may encourage.

PrEP-skeptical physicians have concerns other than just increased promiscuity, though. They’re also less likely to be confident in the drug’s safety. Scientists at the National Institutes of Health feel differently, however, citing no serious side effects of taking the medication. The following insight could explain the discrepancy: the doctors that are least likely to adopt PrEP also tend to have the lowest self-rated knowledge of how it works.

These skeptical providers garner little sympathy from the Human Rights Campaign (HRC), the largest LGBT rights group in the US. The group refers to these reservations about PrEP as “misconceptions” and even suggests ways to push back if your doctor won’t prescribe you the treatment. And HRC isn’t the only force pushing for more PrEP adoption; the CDC also takes issue with the fact that high-risk US populations are not getting enough access to the medication.

While several major US organizations strongly advocate for PrEP adoption in their country, the battle against HIV is far from just an American one. Many other countries are faring much worse. A fifth of people living in Swaziland, for example, have HIV. And as of 2017, 37 million people have the disease worldwide. PrEP could be crucial artillery in preventing further spread of HIV, both in the US and across the world.

But we shouldn’t confuse PrEP with a vaccine that could end the epidemic globally with one shot. High-risk populations around the world will have to take the treatment daily for it to work. Speaking of which, it’s a new day. I need to take another pill.

Jordan Wilkerson is a Ph.D. student in the Chemistry and Chemical Biology program at Harvard University.

Aparna Nathan is a second-year Ph.D. student in the Bioinformatics and Integrative Genomics Ph.D. program at Harvard University. You can find her on Twitter as @aparnanathan.

For more information:

Here are thorough overviews of HIV/AIDS (National Institutes of Health) and PrEP(Center for Disease Control and Prevention).

]]>March 27 – Energy: Where We Get It and Where We Are Goinghttp://sitn.hms.harvard.edu/seminars/2019/march-27-energy-get-going/
Thu, 21 Mar 2019 12:06:44 +0000http://sitn.hms.harvard.edu/?p=15822Time: 7:00-9:00 p.m., Wednesday, March 27th Location: Pfizer Hall at Harvard University, 12 Oxford Street, Cambridge (link to directions) Speakers: Emily Kerr Graphics: Aparna Nathan How do you know that your light will definitely turn on within seconds of your flicking the switch? Ready and reliable access to energy has dramatically changed how human beings live their lives. In this talk, we will discuss how humans have harnessed …

How do you know that your light will definitely turn on within seconds of your flicking the switch? Ready and reliable access to energy has dramatically changed how human beings live their lives. In this talk, we will discuss how humans have harnessed nature’s energy resources and how in turn these resources have impacted our lives. We will look at the systems that get electricity into our homes and workspaces, and the consequences of those systems. Finally we will discuss how we can responsibly meet our energy needs in the future.

The Sun emits enough power onto Earth each second to satisfy the entire human energy demand for over two hours. Given that it is readily available and renewable, solar power is an attractive source of energy. However, as of 2018, less than two percent of the world’s energy came from solar. Historically, solar energy harvesting has been expensive and relatively inefficient. Even this meager solar usage, though, is an improvement over the previous two decades, as the amount of power collected from solar energy worldwide increased over 300-fold from 2000 to 2019. New technological advances over the last twenty years have driven this increased reliance on solar by decreasing costs, and new technological developments promise to augment this solar usage by further decreasing costs and increasing solar panel efficiency.

Solar Cells: Costs, Challenges, and Design

Over the past 20 years, the costs associated with solar cells, the structures capable of converting light energy into electricity, have been steadily decreasing. The National Renewable Energy Laboratory, a US government lab that studies solar cell technology, estimates contributors to the increasing affordability of solar. They estimate that hard costs, the costs of the physical solar cell hardware, and soft costs, which include labor or costs to obtain required government permits, are about equal (Figure 1). Soft costs have decreased because there are more potential consumers and more installation experts for new solar cells, so companies can produce solar cells in bulk and install them easily. Hard costs are less than half of what they were in the year 2000, mostly due to decreasing material costs and an increased ability of cells to capture light. Engineering more cost-effective and efficient solar cells has required careful consideration of the physics involved in solar capture in addition to innovative design.

Figure 1: Costs associated with solar power. Solar cells become less expensive when the cost of the labor and materials use to build them go down, or when they become better at turning incoming light into electricity.

Because solar cells are used to convert light into electricity, they need to be composed of some material that’s good at capturing energy from light. This material can be sandwiched between two metal plates which carry the electricity captured from light energy to where it is needed, like the lights of a home or machines of a factory (Figure 2). Choosing the right material to capture light involves measuring the difference between two energy levels called the valence band and the conduction band. The lower-energy valence band is filled with many small negatively charged particles called electrons, but the higher-energy conduction band is mostly empty. When electrons are hit with particles of light, called photons, they can absorb enough energy to jump from the low-energy conduction band into the high-energy valence band. Once in the valence band, the extra energy in the electron can be harvested as electricity. It’s as if the electrons are sitting at the bottom of a hill (the conduction band) and being hit by a photon that gives them the energy to leap to the top (the valance band).

The amount of energy needed for electrons to jump into the valence band depends on the type of material. Essentially, the size of the metaphorical hill varies based on the properties of a given material. The size of this energy gap matters because it impacts how efficiently solar cells convert light into electricity. Specifically, if photons hit the electrons with less energy than the electron needs to jump from the valence band to the conduction band, none of the light’s energy is captured. Alternatively, If the light has more energy than is needed to overcome that gap, then the electron captures the precise energy it needs and wastes the remainder. Both of these scenarios lead to inefficiencies in solar harvesting, making the choice of solar cell material an important one.

Historically, silicon has been the most popular material for solar cells (Figure 2). One reason for this popularity lies in the size of the gap between silicon’s conduction and valence bands, as the energy of most light particles is very close to the energy needed by silicon’s electrons to jump the energy gap. Theoretically, about 32% of light energy could be converted into electric energy with a silicon solar cell. This may not seem like a lot, but it is significantly more efficient than most other materials. Additionally, silicon is also inexpensive. It is one of the most abundant elements on earth, and the cost of refining it has decreased dramatically since 1980. The solar cell and electronics industries have driven the decrease in purification cost as they have learned better bulk purification techniques to drive the demand of solar cells and consumer electronics.

Figure 2: Light energy capture in solar cells. When light hits a solar cell, it causes it causes electrons to jump into a conduction band, allowing the light energy to be harvested. Here yellow electrons (labeled e) move through the silicon atoms (labeled Si) in the solar cell when hit by a photon.

In addition to decreasing material costs, clever engineering tricks are pushing the efficiency of silicon solar cells closer to their theoretical maximum. In order for photons to be converted into energy, they must first collide with an electron. One trick to increase the likelihood of a photon/electron collision involves patterning the silicon in solar cells in microscopic pyramid shapes. When light is absorbed into a pyramid, it travels further, increasing the probability that the light will collide with the electrons in the silicon before escaping the cell.

In a similar tactic, chemists and material scientists have designed anti-reflective coatings to put on the front of solar cells to prevent useful light from being reflected back into space without ever hitting an electron in the solar cell. Likewise, putting a reflector on the back of the solar cell also allows more light to be harvested. The light that reaches the solar cell and makes it all the way through to the back without hitting an electron gets bounced to the front of the cell, giving the cell another chance of collecting the light.

Currently, the cost of silicon-based solar cells continues to decrease, and, despite predictions to the contrary, the cost of silicon itself continues to decrease. Silicon solar cells are likely to remain popular for the next few years. Alternatives to silicon solar cells have been developed but aren’t far enough along to be commercially viable.

The Future of Solar Cells

To outpace current solar cells, a new design would need to be able to capture more light, transform light energy to electricity more efficiently, and/or be less expensive to build than current designs. Energy producers and consumers are more likely to adopt solar power if the energy it produces is equally or less expensive than other, often non-renewable, forms of electricity, so any improvement to current solar cell designs must bring down overall costs to become widely used.

The first option, adding hardware that allows the solar cells to capture more light, does not actually require that we abandon current solar cell designs. Electronics can be installed with the solar cell that let the cell track the sun as it moves through the daytime sky. If the solar cell is always pointing at the sun, it will be hit by many more photons than if it was only pointing towards the sun around midday. Currently, designing electronics that can track the position of the sun accurately and consistently for several decades at a reasonable cost is an ongoing challenge, but innovation on this front continues. An alternative to making the solar cell itself move is to use mirrors to focus light on a smaller, and therefore cheaper solar cell.

Another route to improving the performance of solar cells is to target their efficiency so they are better at converting energy in sunlight to electricity. Solar cells with more than one layer of light-capturing material can capture more photons than solar cells with only a single layer. Recently, lab-tested solar cells with four layers can capture 46% of the incoming light energy that hit them. These cells are still mostly too expensive and difficult to make for commercial use, but ongoing research may one day make implementing these super-efficient cells possible.

The alternative to improving the efficiency of solar cells is simply decreasing their cost. Even though processing silicon has become cheaper over the past few decades, it still contributes significantly to the cost of solar cell installation. By using thinner solar cells, material costs decrease. These “thin-film solar cells” use a layer of material to harvest light energy that is only 2 to 8 micrometers thick, only about 1% of what is used to make a traditional solar cell. Much like cells with multiple layers, thin-film solar cells are a bit tricky to manufacture, which limits their application, but research is ongoing.

In the immediate future, silicon solar cells are likely to continue to decrease in cost and be installed in large numbers. In the United States, these cost decreases are anticipated to increase the solar power produced by at least 700% by 2050. Meanwhile, research on alternative designs for more efficient and less expensive solar cells will continue. Years from now, we are likely to see alternatives to silicon appearing on our solar farms and rooftops, helping to provide clean and renewable sources of energy. These improvements have and will continue to be made possible by increasing bulk manufacturing of solar cells and new technologies that make the cells cheaper and more efficient.

For more information:

This article is part of our SITN20 series, written to celebrate the 20th anniversary of SITN by commemorating the most notable scientific advances of the last two decades. Check out our other SITN20 pieces!

]]>Does This Meme Really Liken German-Occupied Poland in 1944 with the U.S. in 2018?https://www.snopes.com/fact-check/does-this-meme-really-liken-german-occupied-poland-in-1944-with-the-u-s-in-2018/
Thu, 21 Mar 2019 00:55:49 +0000https://www.snopes.com/fact-check/does-this-meme-really-liken-german-occupied-poland-in-1944-with-the-u-s-in-2018/Trump: Let Mueller Report Come Out, ‘Let People See It’https://www.snopes.com/ap/2019/03/20/trump-let-mueller-report-come-out-let-people-see-it/
Wed, 20 Mar 2019 23:20:36 +0000https://www.snopes.com/ap/2019/03/20/trump-let-mueller-report-come-out-let-people-see-it/Poll: More Americans Want Immigration to Stay the Samehttps://www.snopes.com/ap/2019/03/20/poll-more-americans-want-immigration-to-stay-the-same/
Wed, 20 Mar 2019 23:06:46 +0000https://www.snopes.com/ap/2019/03/20/poll-more-americans-want-immigration-to-stay-the-same/Future Widespread Water Shortage Likely in U.S.http://sitn.hms.harvard.edu/flash/2019/widespread-water-shortage-likely-in-u-s-caused-by-population-growth-and-climate-change/
Wed, 20 Mar 2019 17:55:59 +0000http://sitn.hms.harvard.edu/?p=15771By 2071, nearly half of the 204 fresh water basins in the United States may not be able to meet the monthly water demand. These model projections, recently published in the journal Earth’s Future, are just one preliminary component of the upcoming Resources Planning Act (RPA) Assessment expected to be published next year. In 1974, congress required that this assessment of US renewable resources be …

]]>By 2071, nearly half of the 204 fresh water basins in the United States may not be able to meet the monthly water demand. These model projections, recently published in the journal Earth’s Future, are just one preliminary component of the upcoming Resources Planning Act (RPA) Assessment expected to be published next year. In 1974, congress required that this assessment of US renewable resources be published every 10 years.

Conducted by the U.S. Forest Service, the research describes two causes for the projected shortages. The first is that the U.S. will simply have more people. Despite that the average American is using less water, population growth is still expected to increase water demand across most of the country.

Second, the water supply itself is expected to decrease. Projected climate change affects both rain patterns and temperatures. While rainfall is expected to increase in some parts of the US, the southern Great Plains and parts of the South won’t be so lucky. The water basins rely on rainfall to feed the rivers and tributaries that flow into them. Separately, more water will evaporate from reservoirs and streams as the climate gets warmer, further chipping away at the water supply. Around 50 years from now, many U.S. regions may see water supplies reduced by a third of their current size, while demand continues to increase.

The water shortages may especially impact U.S. agriculture. Irrigated agriculture often accounts for around 75% of the annual consumption of water from these basins. The authors point out, though, that this also makes agriculture a clear area for reducing water use. Up to 96 fresh water basins are projected to face shortages. Reducing water use for irrigation by just 2% could prevent shortages in a third of these basins. For others, though, the reduction must be greater – often over 30%. The authors say it’s unlikely that agriculture will be the only facet of society to adapt. Still, the agricultural sector “is likely to face serious challenges.” Accordingly, the findings raise concerns about both future water security and food security in the U.S.

Managing Correspondent: Jordan Wilkerson

Original Report: Adaptation to Future Water Shortages in the United States Caused by Population Growth and Climate Change. Earth’s Future

]]>The facts on sugar and chronic disease: Four new tools to help you communicate the riskshttps://youracnepro.com/the-facts-on-sugar-and-chronic-disease-four-new-tools-to-help-you-communicate-the-risks/
Wed, 20 Mar 2019 15:32:01 +0000https://youracnepro.com/the-facts-on-sugar-and-chronic-disease-four-new-tools-to-help-you-communicate-the-risks/Sea Otters Leave an Archaeological Record of Their Tool Usehttp://sitn.hms.harvard.edu/flash/2019/sea-otters-leave-archaeological-record-tool-use/
Wed, 20 Mar 2019 12:48:12 +0000http://sitn.hms.harvard.edu/?p=15790Archaeologists learn about ancient humans by excavating and analyzing historical artifacts. While the use of tools was once thought to be a uniquely human trait, this is far from the case; many terrestrial animals, including chimpanzees, macaque monkeys, and even vultures use stone tools to hunt and gather food. For aquatic animals, however, these behaviors have been difficult to observe in the wild. One exception …

]]>Archaeologists learn about ancient humans by excavating and analyzing historical artifacts. While the use of tools was once thought to be a uniquely human trait, this is far from the case; many terrestrial animals, including chimpanzees, macaque monkeys, and even vultures use stone tools to hunt and gather food. For aquatic animals, however, these behaviors have been difficult to observe in the wild. One exception is sea otters, which use large stone “anvils” found along the seashore as tools to smash open mussels that are too difficult to open with their paws. By combining techniques from zoology and archaeology, “animal archaeologists” are beginning to learn more about the history of sea otter tool use.

In a new study, an international group of biologists and archaeologists tracked the mussel eating behavior of sea otters at California’s Bennett Slough Culverts site over a 10-year period. They found that otters used anvils to open around 20% of the mussels they captured, leaving behind a stereotypical damage pattern on the anvils, distinct from human use or weather erosion. When using anvils, otters preferentially targeted water-facing points and ridges as pounding surfaces, rather than flat or land-facing surfaces. Additionally, the discarded mussel shells found around the anvils had a consistent diagonal fracture on their right side, indicating that sea otters smash open their dinner with a characteristic motion (and that they are predominantly right-handed)!

Once an abundant species in the wild, sea otters have experienced a dramatic fall in numbers due to the fur trade. By uncovering the archaeological signature of stone anvil use, scientists are now poised to better track the migration patterns of this now endangered species, as well as date how far back in time anvil use goes. More broadly, further work in the burgeoning field of animal archaeology may reveal the evolution of additional rare animal behaviors.

Managing Correspondent: Benjamin Andreone

News Article: Archaeological Evidence Shows How Animals Are Mastering The Use Of Stone Tools. Forbes

]]>Arrival of Gene-Edited Babies: What lies ahead?http://sitn.hms.harvard.edu/flash/2019/arrival-gene-edited-babies-lies-ahead/
Mon, 18 Mar 2019 13:00:42 +0000http://sitn.hms.harvard.edu/?p=15783by Valentina Lagomarsino figures by Sean Wilson Nearly four months ago, Chinese researcher He Jiankui announced that he had edited the genes of twin babies with CRISPR. CRISPR, also known as CRISPR/Cas9, can be thought of as “genetic scissors” that can be programmed to edit DNA in any cell. Last year, scientists used CRISPR to cure dogs of Duchenne muscular dystrophy. This was a huge step forward for …

Nearly four months ago, Chinese researcher He Jiankui announced that he had edited the genes of twin babies with CRISPR. CRISPR, also known as CRISPR/Cas9, can be thought of as “genetic scissors” that can be programmed to edit DNA in any cell. Last year, scientists used CRISPR to cure dogs of Duchenne muscular dystrophy. This was a huge step forward for gene therapies, as the potential of CRISPR to treat otherwise incurable diseases seemed possible. However, a global community of scientists believe it is premature to use CRISPR in human babies because of inadequate scientific review and a lack of international consensus regarding the ethics of when and how this technology should be used.

Early regulation of gene-editing technology

In 1972, Paul Berg, an American scientist, took genetic material from one cell and inserted it into the genome of another cell with a virus, generating the first recombinant DNA molecule (Figure 1). This new gene-editing technology allowed for rapid advancements in science, medicine, and agriculture, but it was met with strong pushback on the putative hazards of genetic modification. In 1975, the National Institutes of Health (NIH) appointed a Recombinant DNA Advisory Committee (RAC), a group of 25 scientists tasked with creating the NIHGuidelines for Research Involving Recombinant DNA Molecules. The RAC’s principal mandate was to serve as an advisory committee—to review research proposals planning to genetically modify cells and to withhold funding from projects that did not follow the evolving Guidelines.

Figure 1: Recombinant DNA Technology. DNA from one cell (purple) is transferred into the DNA of the second cell (blue) using a virus.

In the late 1980s, the RAC first began approving clinical trials using recombinant DNA technology to genetically engineer somatic cells. Somatic gene therapy refers to genetic modifications made in non-reproductive cells so the modifications are not passed onto future generations (Figure 2). Today, there are thousands of clinical trials utilizing somatic cell gene therapy with recombinant DNA technology to treat disease. Contrary to somatic gene therapy, in the mid 1990s, national and international guidelines and regulations were established in over 40 countries to prohibit germline genome editing in humans. Germline genome editing is controversial because it makes permanent changes to parental egg or sperm cells in humans that can be inherited in all future generations (Figure 2). A common fear is that germline genome editing may also lead down a “slippery slope” towards designer babies.

Figure 2: Somatic Cells vs. Germline Cells. DNA editing made in somatic cells (purple) cannot be passed down to future generations. DNA editing made in germline cells (gray) will be passed down to all further generations.

Advent of CRISPR: Genome editing 2.0

In 2012, 40 years after the initial development of recombinant DNA technology, scientists uncovered the powers of CRISPR to edit the genome of mammalian cells. CRISPR is a much faster and effective way to edit the genome of any cell, but it may cause unintended DNA changes. Given the potential of CRISPR to more easily modify the genome, Congress passed a bill in 2015 that prohibits the Food and Drug Administration (FDA) from reviewing any drug or biological product in which a human embryo has been genetically modified (Figure 3). There were also many international policies discussed in 2015, including one proposed by the United Nations Educational, Scientific and Cultural Organization (UNESCO) which called for a moratorium on germline genome editing, but none of these policies became international law. Two days after He Jiankui’s announcement that he had successfully used CRISPR to conduct germline gene editing, in November of 2018 scientists met for the Second International Summit on Human Genome Editing in Hong Kong. Many criticized He’s work, both for a “lack of oversight and transparency” and for a lack of rigorous experiments addressing the safety of germline genome editing. Recently, a group of distinguished international scientists, including scientists who contributed to the discoveries of recombinant DNA and CRISPR, have called for a “global moratorium on all clinical uses of human germline editing.”

In 2003, following a rise in assisted reproductive technologies, the Chinese Ministry of Health delivered a set of Guidelines for conducting research on embryonic cells (Figure 3). These guidelines, which some believe are not sufficient in the CRISPR era, discourage using viable embryos for research but specify no explicit penalties. After the news about CRISPR babies broke in November 2018, the Chinese Academy of Medical Sciences responded, stating, “We are opposed to any clinical operation of human embryo genome editing for reproductive purposes in violation of laws, regulations, and ethical norms in the absence of full scientific evaluation.” At present, it is unclear if these guidelines will change in China or whether the Ministry will adopt a different regulatory system. In the US, the National Institutes of Health (NIH) director, Francis Collins, responded by saying, “Maybe what we need is a new version of the RAC that allows a public, intense, scientific debate about areas of some scientific potential where there are many unknowns.” On an international level, the World Health Organization (WHO) has established an expert panel for oversight of human genome editing, a group that plans to review gene-editing globally and hopes to establish a governing framework for germline gene-editing technologies.

Figure 3: International Regulatory Landscape on Germline Genome Editing. Many countries have longstanding legislation in place to prohibit germline genome editing. The US congress banned the FDA from approving any therapy involving germline genome editing in 2015 and this law was renewed in 2018 (Sec. 736). China has had regulatory guidelines in place since 2003, but these regulations have not been updated since. Countries colored in gray have ambiguous regulations, and we do not have sufficient data to categorize countries in white. Image adapted from Araki M and Ishii T, 2014. and Ishii T, 2015.

Ethical Considerations—Why & Who

One of the greatest debates on the ethics of germline genome editing surrounds the reasons why we are using this technology: for therapeutic interventions in dire circumstances or for the enhancement of humanity? This international debate is complicated because of the cultural differences in perspective on what should receive a genetic therapeutic intervention. When cochlear implants were first invented, members of the deaf community protested, stating “What may seem to a hearing person as opportunity may be seen by some deaf people as a loss.” The rise of genetic engineering may open a door to eliminate traits that some cultures—but not others—consider an illness or deficit. Moreover, some bioethicists believe that if we do not draw a clear line between therapy and enhancement, we may usher in a new wave of eugenics.

There is another issue for the international community to address: Who will have access to CRISPR therapies? Currently, the easiest avenue for editing the germline is through in vitro fertilization (IVF), which can be quite expensive. In developing countries around the world, access to IVF clinics is greatly limited; in the US, health insurance companies rarely cover the costs of IVF, which can be $20,000 or more. Politicians discussing health care reform will not only have to consider who has access to basic primary health care needs, but also whether socioeconomic status will be etched in the genes of people who cannot afford gene-editing therapies to have undesirable genes removed.

Scientists and the public across the globe now need to decide how to move forward with CRISPR/Cas9; this tool has the potential to save many lives and improve quality of life, yet we must also reckon with the power of controlling the DNA of generations to come.

Valentina Lagomarsino is a first-year graduate student in the Biological Biomedical Sciences Ph.D. program at Harvard University.

Sean Wilson is a fifth-year graduate student in the Department of Molecular and Cellular Biology at Harvard University.

Cover Image: Illustration by David Parkins; used with permission of the illustrator. A version of this graphic has also appeared in the journal Nature.

]]>FDA approves first ketamine-based antidepressanthttp://sitn.hms.harvard.edu/flash/2019/fda-approves-first-ketamine-based-antidepressant/
Thu, 14 Mar 2019 14:00:35 +0000http://sitn.hms.harvard.edu/?p=15755Depression is the leading cause of disability worldwide, affecting more than 300 million people of all ages around the world. The most commonly used antidepressant medications are called selective serotonin reuptake inhibitors (SSRIs). Only about one third of people with major depressive disorder achieve remission after treatment with SSRIs. When the first medication doesn’t work, the next steps are usually to switch to or add another …

]]>Depression is the leading cause of disability worldwide, affecting more than 300 million people of all ages around the world. The most commonly used antidepressant medications are called selective serotonin reuptake inhibitors (SSRIs). Only about one third of people with major depressive disorder achieve remission after treatment with SSRIs. When the first medication doesn’t work, the next steps are usually to switch to or add another SSRI medication. After trying different options or combinations, almost 70% of people with depression will be able to achieve remission. Unfortunately, the remaining 30% of people will not be able to find a treatment that works, and are said to have treatment resistant depression.

Ketamine was first approved for use as an anesthetic in 1970 and was later abused as a party drug, thereby creating a stigma surrounding its use in a medical setting. After a series of studies in the early 2000s, scientists began investigating ketamine for its rapid-acting antidepressant effects. Subsequent studies showed promising results and, last week, the FDA approved the use of the nasal spray Spravato, the first ketamine-based antidepressant for patients who haven’t responded to two or more SSRI antidepressants. Unlike SSRIs, which can take weeks or months to begin taking effect, a single dose of ketamine was found to produce antidepressant effects within a few hours and lasted at least one week after the single treatment. To avoid recreational use of the medication, the FDA has only made the drug available through a restricted distribution system. The drug will be administered under supervision of healthcare professionals and patients will be monitored for two hours after treatment for potential side effects.

In a space that has been limited to the use of SSRIs,this opens up many new opportunities for the treatment for depression. At the same time, safety and caution are very important. Typically, antidepressants are approved on the basis of two positive short-term trials. However, since the benefits outweighed the associated risks, the FDA advisory committee voted to approve the drug after only one positive trial. Additional, larger clinical trials are needed to assess long term safety and efficacy of ketamine-based antidepressants. It will also be important to maintain perspective throughout the hype around ketamine in the media. In the excitement, patients have begun to think of ketamine as a miracle drug, requesting it before standard SSRI treatments. Whether ketamine-based antidepressants are more effectivethan SSRIs, for safe and successful treatment of depression, remains to be investigated.

]]>CRISPR-Scanning Towards New Drugs — drug discovery is difficult, but CRISPR might be able to helphttp://sitn.hms.harvard.edu/flash/2019/crispr-scanning-towards-new-drugs-drug-discovery-is-difficult-but-crispr-might-be-able-to-help/
Thu, 14 Mar 2019 12:15:04 +0000http://sitn.hms.harvard.edu/?p=15772by Michael Vinyard figures by Nicholas Lue Most therapeutic drug candidates that are put through clinical trials fail. Given that most of these fail during early development, the cost of bringing a single drug to market is now over $2.5 billion. If we focus on cancer alone, this high cost of drug development, combined with the fact that cancer is one of the leading killers in …

Most therapeutic drug candidates that are put through clinical trials fail. Given that most of these fail during early development, the cost of bringing a single drug to market is now over $2.5 billion. If we focus on cancer alone, this high cost of drug development, combined with the fact that cancer is one of the leading killers in the US, means that any acceleration in cancer drug discovery could save lives. CRISPR-Cas9, the recently-harnessed genome editing technology, might find itself as a driver of such an acceleration.

CRISPR-Cas9 technology

CRISPR-Cas9 has been making waves in scientific communities for the past several years. It is a bio-engineering tool that enables genetic editing. In other words, this tool can be used to make physical cuts in our genetic material, DNA, creating changes called mutations. DNA is composed of many units, called genes, that provide a set of instructions for making proteins, which are the molecules that execute the functions necessary for life. For instance, proteins do the work that allows our muscles to move and our hearts to pump, as well infinitely more minute yet vital actions inside of every cell in the body.

This direst relationship between DNA/genes, protein, and human health is what makes CRISPR-Cas9 technology so exciting. When CRISPR is used to create a mutation in the DNA sequence, this mutation will be propagated to the protein product, which can impact the health of the cell and the person as a whole (Figure 1). For example, to directly reverse certain genetic diseases, CRISPR-Cas9 can theoretically be used to cut disease-causing genes, altering that gene’s protein product and ameliorating disease symptoms. In addition to these therapeutic aims, researchers have also been exploring CRISPR-Cas9’s use as a tool in drug discovery.

Figure 1: CRISPR-Cas9 induces lesions in DNA that are propagated to proteins. Cas9 is used to cut DNA, generating lesions or scars (panel A). RNA, an intermediary between DNA and protein, retains these CRISPR-Cas9-mediated scars, which are indicated by colored segments (panel B). RNA is used as instructions to make protein by the cell. The colored portions indicate the mutated parts of the protein (panel C).

CRISPR-Cas9 as a drug discovery tool

Therapeutic drugs, such as those intended to treat cancer, work by altering the function of the body’s workforce: proteins. In order to create such a drug, the first step is to determine which proteins should be targeted. In other words, which proteins actually matter for, say, the formation of cancer? To find these disease-relevant genes and proteins, researchers can use CRISPR-Cas9 to systematically inactivate, or knock out, the ~20,000 protein-coding genes found in humans. This approach is commonly referred to as a “genome-wide screen.”

For example, one might imagine investigating tumor formation in mice. To better understand which genes are responsible for driving the growth of a specific cancer, researchers can use CRISPR to remove, one by one, nearly every gene in these cancer cells. This approach allows them to identify a subset of genes that, when removed using CRISPR, block tumor formation. This information then can then be used to inform drug development. Specifically, if a drug could be designed that inactivates these proteins, identified by CRISPR as being necessary for tumor formation, then this could represent a very effective anti-cancer therapy.

While CRISPR’s role in identifying disease-related proteins is very useful, this is only the first step. This is because proteins are complex molecules that contain various parts, also known as domains. This is similar to a car that contains many parts, some of which are more important to the critical function of driving than others. If you take the doors off of a car, chances are it will still run. However, if you take the wheels off, things might be a little more difficult. All the same with proteins; if you mess up an accessory portion, it might still work; if you mess up a critical portion, it might be fatal. When researchers are designing drugs, they often look for those that might target critical regions of a protein. In the process of identifying lead anti-cancer drug candidates, researchers often modify the target protein to better understand which parts of the target are most critical to the interaction with the drug molecule. To do this, researchers have again turned to the power of CRISPR-Cas9 technology.

CRISPR-scanning

CRISPR-scanning is an approach that uses the cutting ability of CRISPR to make lesions across a gene that encodes a particular protein of interest. Rather than try to make a precise genome edit, CRISPR-scanning cuts DNA and then uses the cells’ built-in DNA repair machinery to fuse the DNA back together, making an imperfect and somewhat random scar. These scars are used as part of the instructions to make proteins. So, when CRISPR is used to generate many mutant versions of a gene, this generates many mutant versions of the corresponding protein, which can be studied to determine which parts of the protein matter for its function. So, for example, by sequentially mutating every domain in a protein, scientist can figure out which parts are the metaphorical doors, and which parts are the wheels. This distinction will allow for the design of drugs that target the important parts of proteins, like those that contribute to tumor formation. In other words, CRISPR-scanning can identify the exact region of a protein that a therapeutic drug might do well to attach itself to in order to inactivate the protein.

CRISPR-scanning can also be done in the presence of a drug (CRISPR-suppressor scanning). If a drug is any good, it kills cancer cells. In this context, researchers can observe the extent to which cells containing various genetic scars thrive despite the presence of a drug. If a mutation caused by a scar prevents a drug from binding, the growth of that cancer cell might be rescued and cells with that scar will multiply (Figure 2). This is useful because part of making a good drug (or set of drugs) is knowing what might defeat it – cancer is a notoriously adaptable disease and one of the pitfalls of several cancer drugs is the development of cancer-resistance. Generating and studying this drug-resistance in the lab, before a drug ever gets to humans, is thus extremely useful. This is different than simple CRISPR-scanning in that instead of the interesting cells being those that died, it is those that thrive in the presence of a drug that normally kills them, due to their new CRISPR-induced mutation. Information about which protein regions, when mutated, lead to cell growth or cell death can be overlaid onto the 3-D structure of the protein target and drug-interacting hotspots can be identified. As such, the ability of CRISPR to identify which parts of the protein are important for function or disrupt the drug’s ability to engage its target make this technology an indispensable tool for therapeutic development.

Figure 2: CRISPR-suppressor scanning. The blue object represents a drug. The white shapes represent a hypothetical target protein. The colored portions of the proteins indicate the mutated portions of the protein. The magenta mutation happens to be located in the drug binding site and prevents the drug from binding, whereas in the other two (red and orange) examples, the mutation does not interfere with drug binding. In the case of the magenta mutation, the drug is blocked and the cell lives and multiplies.

CRISPR will aid biological discovery and will likely help us find new drugs

CRISPR genome editing is relatively new technology and, while its use in research laboratories as a tool is now widespread, the use of this technology in a living human is still considerably risky, especially given its irreversible nature and the number of safety trials it has yet to undergo. CRISPR-scanning and CRISPR-suppressor scanning have the opportunity to leverage CRISPR genome editing by taking advantage of its strengths, such as its programmable ability to alter DNA. Both strategies hold promise as new players in the drug discovery pipeline and may play a key role in the development of many future therapies. As a whole, it is my opinion that CRISPR may be the catalyst that helps us find more drugs for diseases like cancer and may indirectly save many lives through the research it enables.

Michael Vinyard is a third-year PhD student at Harvard University in the Department of Chemistry and Chemical Biology. He has been studying the role of chromatin regulators in cancer biology through CRISPR screens and other functional genomics and molecular biology-based approaches.

Nicholas Lue is a graduate student in the Chemical Biology PhD program at Harvard University. You can find him on Twitter as @nicklue8.

For more information:

A recent open-access review of the “CRISPR tool kit” available to researchers can be found here.

Here is a very brief writeup on the first instance of CRISPR-scanning being used in the lab of Professor Chris Vakoc at Cold Spring Harbor Laboratories.

A more practical explanation of a genome-wide screen can be found here.

This article is part of our SITN20 series, written to celebrate the 20th anniversary of SITN by commemorating the most notable scientific advances of the last two decades. Check out our other SITN20 pieces!

]]>Jellyfish-inspired electronic skin can heal itself under waterhttp://sitn.hms.harvard.edu/flash/2019/jellyfish-inspired-electronic-skin-can-heal-water/
Wed, 13 Mar 2019 17:00:08 +0000http://sitn.hms.harvard.edu/?p=15760Skin is the largest organ in human body, and can sense important information such as pressure, temperature and pain. This waterproof barrier protects us from infections and can heal itself. Electronic skins are soft and flexible electronics that mimic the functions of skin in one or multiple aspects, and can give robots or even prosthetic limbs the sensations of real skin. However, unlike real skin, …

]]>Skin is the largest organ in human body, and can sense important information such as pressure, temperature and pain. This waterproof barrier protects us from infections and can heal itself. Electronic skins are soft and flexible electronics that mimic the functions of skin in one or multiple aspects, and can give robots or even prosthetic limbs the sensations of real skin. However, unlike real skin, electronics lack the ability to heal after sustaining damage, nor can they perform normal functions under water. Inspired by jellyfish, scientists from Tsinghua University and National University of Singapore developed an electronic skin material that can restore functions after sustaining damage in wet environments.

This gel-like, aquatic, stretchable, self-healing electronic skin, or ‘GLASSES’, is made from two components, a polymer and an ionic liquid, that strongly interact with each other. After cutting the material in half, the polymer can bridge across the damaged interfaces, provided there’s a small enough gap, and heal the damage. The two components are water-resistant, and thus can restore the original electrical and mechanical properties both in air and underwater. To demonstrate its basic functions as an electronic skin, the GLASSES material has been used to make touch, pressure and strain sensors.

This work represents an important step in the development of electronic skins, and may one day be used to develop aquatic soft robots that can sense the environment and are robust enough to recover from mechanical damage. Future development of this material should focus on improving the performance of the sensors and incorporating different types of electronics to match the functionalities of the real skin.

]]>Health24.com | Hydration: how much is too much?https://youracnepro.com/health24-com-hydration-how-much-is-too-much/
Wed, 13 Mar 2019 15:15:04 +0000https://youracnepro.com/health24-com-hydration-how-much-is-too-much/A New Kind of Twinhttp://sitn.hms.harvard.edu/flash/2019/new-kind-twin/
Mon, 11 Mar 2019 14:13:17 +0000http://sitn.hms.harvard.edu/?p=15752Researchers in Australia have found the second-ever documented case of semi-identical twins, who share all the DNA from their mother but have different sets of genes from their father. A potential mechanism for such an uncommon occurrence is the fertilization of a single egg by two sperm cells. However, this scenario typically results in an inviable pregnancy, raising the question of what specific conditions allowed for the proper development of these twins.

]]>Sets of twins are commonly grouped into two classes: monozygotic, or identical; and dizygotic, or fraternal. Identical twins result from a fertilized egg (an egg that has fused with a sperm cell) dividing in two. Both newly identical fertilized eggs can then go onto to develop into their own organisms, sharing identical genes, the functional units of DNA. Fraternal twins are instead the result of two sperm cells each independently fertilizing a separate egg. In this case, the twins share about 50% of their genes, the same as any other set of full siblings, and can have different biological sex, unlike the former case. For the second time ever, a group of researchers in Australia have discovered a pair of “sesquizygotic,” or semi-identical, twins, resulting from a distinct fertilization process.

An ultrasound of a pregnant woman at 6 weeks showed a set of monochorionic twins, which share the same placenta, an observation typically indicative of identical twins. Eight weeks later, however, a subsequent test showed that the twins were of different biological sex. As sex is determined by one’s genes, and identical twins share all their genes, this contradicts the above results, instead suggesting the twins were fraternal. A set of DNA sequencing tests were then conducted, revealing that the twins shared identical sets of maternal DNA but only 78% of paternal DNA, placing them somewhere between identical and fraternal.

A likely cause of the above scenario is polyspermy, in which one egg is fertilized by multiple sperm cells. In this case, the egg carrying the maternal DNA is shared between the twins, while the different sperm cells allow for segregation of paternal DNA such that the set given to each developing fetus is distinct. While biologists have known that eggs can occasionally be fertilized by multiple sperm cells, this often results in an inviable pregnancy. Therefore, an interesting outstanding question is what specific genetic or environmental conditions allowed this unique case, and perhaps the previously documented one, to remain viable?

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]]>Try these study tips when you are down to the wire!Signup for your FREE trial to The Great Courses Plus here: http://ow.ly/TDjL30nzMVp

Listen to our podcast Sidenote! https://bit.ly/2SYfqcx

"The Great Courses Plus is currently available to watch through a web browser to almost anyone in the world and optimized for the US, UK, and Australian markets. The Great Courses Plus is currently working to both optimize the product globally and accept credit card payments globally."